The mechanical environment of the chondrocytes is an important factor that affects the health and function of the diarthrodial joint. The mechanical signals to which chondrocytes are exposed depend on the biomechanical interactions between the cell, pericellular matrix, and extracellular matrix. Currently, there is little or no information available on the mechanical properties of the pericellular matrix of articular cartilage. The goals of this study are to measure the intrinsic biomechanical and diffusion properties of the chondrocyte pericellular matrix, and to test the hypothesis that these properties are altered in osteoarthritic cartilage. Furthermore, we propose that type VI collagen, which is abundantly present in the pericellular matrix, influences the physical properties of this region. We will use several novel experimental techniques to quantify the micromechanical behavior of pericellular matrix using the isolated chondron model. The Specific Aims of this study are: (1) measure the mechanical properties of the pericellular matrix from normal and osteoarthritic cartilage using micropipette aspiration and atomic force microscopy, incorporate these findings in a theoretical model of cell-matrix interactions in cartilage, and validate these predictions using 3D confocal microscopy; (2) measure the diffusion properties of the pericellular matrix of normal and OA cartilage; (3) determine how the presence of a normal or OA pericellular matrix influences the metabolic response of chondrocytes to dynamic compression within an artificial matrix; and (4) determine what role type VI collagen plays in the mechanical properties of the pericellular matrix. The long-term goals of this study are to improve our understanding of the role of mechanical factors in the regulation of cartilage metabolism in normal and diseased conditions. A better understanding of these pathways will hopefully lead to the development of new pharmaceutical or biophysical interventions for the treatment of osteoarthritis.